The long-range goal of this project is to understand the descending neural systems that control information output from the cochlea and cochlear nucleus to higher brain centers. Among the general hypotheses for the function of descending systems are that 1) they extend the dynamic range of the auditory system, 2) they enable selective attention to signals in noisy environments, and 3) they help to protect the inner ear from overstimulation. Existence of descending innervation to hair-cell systems in virtually every vertebrate species examined thus far is strong presumptive evidence for the importance of these feedback systems. This project will concentrate on one particular descending system, the medial olivocochlear (MOC) system in mammals. MOC neurons send projections from a part of the lower brain, the superior olivary complex, to the outer hair cells of the cochlea. In addition to innervating outer hair cells, MOC neurons give off side branches to both the cochlear nucleus and the vestibular nuclei. The proposed research will investigate which cells in the cochlear nucleus are the target neurons of the MOC branches, how the target neurons are affected physiologically, and which neurotransmitters are likely to be involved in mediating those effects. One approach that will be used in the proposed research is to use transneuronal labeling by the neuronal tracer, horseradish peroxidase (HRP). Preliminary studies indicate that both afferent fibers of the auditory nerve and MOC branches can label their associated cochlear-nucleus neurons when heavily loaded with HRP. Very dense labeling of the primary elements is achievable with very small rodents such as the mouse, our chosen animal model. Transneuronal labeling should yield important new information for the auditory system and for neurobiology in general. Our proposed research will also address the differences found in projections of olivocochlear (0C) fibers to the basal and apical regions of the cochlea. Questions such as the fields innervated by single 0C fibers in both the cochlea and cochlear nucleus will influence theoretical formulations of how the MOC system controls afferent signals sent to more central regions of the brain.